The proposed research is a continuation of previous studies on the inhomogeneity of human and animal hemoglobins. A study of human hemoglobin variants will be made by precise chemical and functional analyses. Results from these studies will give insight into the nature of disease states and the functional properties of normal and variant hemoglobins. It is proposed to continue the extensive analyses of human fetal hemoglobins both in normal and pathological conditions. Data from these analyses will contribute to the basic understanding of disease states, beta-thalassemia, other hemoglobinopathies, and acquired hematological disorders, particularly. These studies will help to define normal mechanisms of protein synthesis and the malfunction of some of these mechanisms in disease. The ultimate goal will be to find means to effectively influence some of these mechanisms, mainly the activation/deactivation mechanism(s) of structural hemoglobin genes. Analyses of the hemoglobins from certain animal species will be made to further define multiplicity of the Hb alpha locus, and to provide data which will measure the relative production of nonallelic structural genes for the alpha chain similarly as is proposed for the nonallelic structural genes for the human gamma chain. Structural analyses of beta chains of deer hemoglobins may provide data useful for the understanding of the mechanism of hemoglobin aggregation both in this animal species and in patients with sickle cell anemia.